This randomized phase III trial studies the best individual therapy for women who have node-negative, estrogen-receptor positive breast cancer by using a special test (Oncotype DX), and whether hormone therapy alone or hormone therapy together with combination chemotherapy is better for women who have an Oncotype DX recurrence score of 11-25. Estrogen can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hormone therapy together with more than one chemotherapy drug (combination chemotherapy) has been shown to reduce the chance of breast cancer recurrence, but the benefit of adding chemotherapy to hormone therapy for women with node-negative, estrogen-receptor positive breast cancer is small. New tests may provide information about which patients are more likely to benefit from chemotherapy.

Disease-free survival [ Time Frame: Date of randomization or registration to the date of ipsilateral breast tumor recurrence, local/regional recurrence, distant recurrence, second primary cancer (breast or non-breast), or death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]

DFS will be compared using a stratified log rank test.

Secondary Outcome Measures:

Distant recurrence-free interval [ Time Frame: Date of randomization or registration to the date of distant recurrence of breast cancer, or of death with distant recurrence, if death is the first manifestation of distant recurrence, assessed up to 10 years ] [ Designated as safety issue: No ]

Compared using a stratified log rank test.

Recurrence-free interval [ Time Frame: Date of randomization or registration to the date of first recurrence of breast cancer (IBTR, LRR, or DR) or to the date of death with recurrence, if death is the first manifestation of recurrence, assessed up to 20 years ] [ Designated as safety issue: No ]

Overall survival [ Time Frame: Date of randomization or registration to date of death from any cause, assessed up to 20 years ] [ Designated as safety issue: No ]

A t-test comparing the 3-month evaluations will have 90% power for a mean difference of 4.5 points (0.3 standard deviations), allowing a two-sided type I error of 5%. Within the postmenopausal and premenopausal subsets, there will be 90% power to detect a mean difference of 5.7 and 7.35 points (0.38 and 0.49 standard deviations), respectively.

Simultaneous confidence intervals for differences over time will be determined from a model where the effects are allowed to vary smoothly over time which gives a reasonable fit to the data. The relationship of cognitive function to outcomes in other domains, such as symptoms of depression and anxiety (assessed by the Hospital Anxiety and Depression Scale) and fatigue (assessed by the FACT fatigue scale) will be evaluated by including the values as (time-dependent) covariates in the longitudinal models.

Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.

Drug: Tamoxifen Citrate

Given PO

Other Names:

ICI 46,474

ICI-46474

Drug: Anastrozole

Given PO

Other Names:

ANAS

ICI-D1033

ZD-1033

Drug: Letrozole

Given PO

Other Names:

CGS 20267

Femara

LTZ

Drug: Exemestane

Given PO

Other Names:

Aromasin

FCE-24304

PNU 155971

Radiation: Radiation Therapy

Undergo radiation therapy or partial breast irradiation

Other Names:

Cancer Radiotherapy

Irradiate

Irradiated

Irradiation

RT

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Quality-of-Life Assessment

Ancillary studies

Other Name: Quality of Life Assessment

Experimental: Group 2, Arm I (experimental)

Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.

Drug: Tamoxifen Citrate

Given PO

Other Names:

ICI 46,474

ICI-46474

Drug: Anastrozole

Given PO

Other Names:

ANAS

ICI-D1033

ZD-1033

Drug: Letrozole

Given PO

Other Names:

CGS 20267

Femara

LTZ

Drug: Exemestane

Given PO

Other Names:

Aromasin

FCE-24304

PNU 155971

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Quality-of-Life Assessment

Ancillary studies

Other Name: Quality of Life Assessment

Active Comparator: Group 2, Arm II (standard)

Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.

Drug: Tamoxifen Citrate

Given PO

Other Names:

ICI 46,474

ICI-46474

Drug: Anastrozole

Given PO

Other Names:

ANAS

ICI-D1033

ZD-1033

Drug: Letrozole

Given PO

Other Names:

CGS 20267

Femara

LTZ

Drug: Exemestane

Given PO

Other Names:

Aromasin

FCE-24304

PNU 155971

Radiation: Radiation Therapy

Undergo radiation therapy or partial breast irradiation

Other Names:

Cancer Radiotherapy

Irradiate

Irradiated

Irradiation

RT

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Quality-of-Life Assessment

Ancillary studies

Other Name: Quality of Life Assessment

Experimental: Group 3 (Oncotype DX recurrence score >= 26)

Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.

Negative axillary nodes: As assessed by a sentinel lymph node biopsy, an axillary dissection, or both, and as defined by the Sixth Edition of the American Joint Committee on Cancer (AJCC) staging criteria

NOTE: Definition of tumor size: The tumor size used for determination of eligibility is the pathologic tumor size, which is usually determined by the size of the tumor as measured by inspection of the gross specimen; if the tumor size is measured microscopically and the tumor includes ductal carcinoma in-situ, the measurement should include only the invasive component of the tumor

The patient and physician must be agreeable to initiate standard chemotherapy and hormonal therapy as adjuvant therapy

A tissue specimen from the primary breast cancer has been located and is ready to be shipped to the appropriate laboratory after consent is obtained and within 3 days following pre-registration; NOTE: For determination of the Oncotype Recurrence Score, tissue must be shipped to Genomic Health; if the Oncotype DX Recurrence Score was previously performed by Genomic Health (prior to pre-registration), tissue must be submitted to the Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) Central Biorepository and Pathology Facility upon randomization

Patients must be disease-free of prior invasive malignancies for >= 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; patients with a previous ipsilateral or contralateral invasive breast cancer, or with bilateral synchronous cancers, are not eligible; patients with previous ipsilateral or contralateral ductal in situ carcinoma (DCIS) are not eligible

Prior treatment

Mandatory prior surgery criteria:

Patient must pre-register within 84 days from the final surgical procedure required to adequately treat the primary tumor (please note that if margins are not clear and a resection has to be conducted after pre-registration but before randomization, the patient will be deemed to be within the 84 day window allowed by protocol and therefore eligible)

All tumors should be removed by either a mastectomy or local excision plus an acceptable axillary procedure (i.e., sentinel lymph node biopsy, axillary dissection, or both); there must be adequate (at least 1 mm if margin width specified) tumor-free margins of resection (for invasive and ductal carcinoma in-situ) in order for the patients to be eligible; patients with lobular carcinoma in-situ involving the resection margins are eligible

Criteria re: other prior treatments:

No prior chemotherapy for this malignancy

No prior radiation therapy for this malignancy; this includes no prior MammoSite Brachytherapy radiation therapy (RT)

Hormonal therapy: Patients who develop breast cancer while receiving a selective estrogen-receptor modulator (SERM; e.g., tamoxifen, toremifene, raloxifene) or an aromatase inhibitor (e.g., anastrazole, letrozole, exemestane) for breast cancer prevention or a SERM for other indications (e.g., raloxifene for osteoporosis) are not eligible; however, patients may have received up to 8 weeks of a SERM or aromatase inhibitor for this malignancy and still be eligible for study entry

Patients must have an anticipated life expectancy of at least 10 years

Patients with the following medical conditions should not be enrolled on the study:

Chronic obstructive pulmonary disease requiring treatment

Chronic liver disease (e.g., cirrhosis, chronic active hepatitis)

Previous history of a cerebrovascular accident

History of congestive heart failure or other cardiac disease that would represent a contraindication to the use of an anthracycline (e.g., doxorubicin or epirubicin)

Chronic psychiatric condition or other condition that would impair compliance with the treatment regimen

Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to pre-registration to rule out pregnancy

Women of childbearing potential must be strongly advised to utilize an accepted and effective form of non-hormonal contraception (e.g. intrauterine device, condoms, diaphragm, abstinence)

Patients must not have previously had the Oncotype DX Assay performed, with the exception of patients who have had the assay performed and have a recurrence score of 11-25

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310180